Target drug and gene delivery are rapidly emerging applications for ultrasound contrast agents since they reduce potential deleterious side effects to healthy tissue and minimize the overall dose needed. Development of new contrast agents requires a good understanding of the effect of the properties of the viscous material of the shell and of the acoustic field on the dynamics of the agent and on the mechanism of breakup of the shell. A novel numerical code, which enables modeling of non-spherical contrast agent's dynamics acoustic waves and nearby boundaries and tissues is proposed. This model, whose feasibility was demonstrated in Phase I, will allow us to accurately predict the necessary conditions for breakup. In Phase I we coupled a Boundary Element Method solver and a Navier-Stokes solver and demonstrated 3D modeling of viscous thick shelled contrast agent including in the presence of rigid walls, and identified the mechanisms for shell breakup due to non-spherical deformations. In the Phase II study, we will complete, improve and expand the capabilities of the model to simulate viscoelastic shell material properties and simulate multiple contrast agents'interactions with deformable boundaries such as blood cells, tissues, and blood vessels. We will also validate the developed model experimentally using both a scaled-up test for visualization and actual contrast agents for breakup limit confirmation. PUBLIC HEALTH RELEVANCE: Success of this research will help pharmaceutical companies develop safer and more efficient drug and gene delivery agents. These agents are especially attractive to chemotherapy treatment because they can greatly reduce deleterious side effects to healthy tissue caused by many chemotherapy drugs and minimize the overall dose needed.